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ACS Medicinal Chemistry Letters最新文献

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Novel Substituted Cyclic Compounds as SLC6A19 Inhibitors for Treating Phenylketonuria and Other Amino Acidurias 新型取代环化合物作为SLC6A19抑制剂治疗苯丙酮尿症和其他氨基酸尿症
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-11 DOI: 10.1021/acsmedchemlett.5c0017710.1021/acsmedchemlett.5c00177
Ram W. Sabnis*, 
{"title":"Novel Substituted Cyclic Compounds as SLC6A19 Inhibitors for Treating Phenylketonuria and Other Amino Acidurias","authors":"Ram W. Sabnis*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0017710.1021/acsmedchemlett.5c00177","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00177https://doi.org/10.1021/acsmedchemlett.5c00177","url":null,"abstract":"<p >Provided herein are novel substituted cyclic compounds as SLC6A19 inhibitors, pharmaceutical compositions, use of such compounds in treating phenylketonuria, and other amino acidurias and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"734–735 734–735"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting KRAS G12D Mutations: Advances in Small Molecule Inhibitors and PROTAC Technology 靶向KRAS G12D突变：小分子抑制剂和PROTAC技术的进展
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 DOI: 10.1021/acsmedchemlett.5c0017910.1021/acsmedchemlett.5c00179
Robert B. Kargbo*, 
{"title":"Targeting KRAS G12D Mutations: Advances in Small Molecule Inhibitors and PROTAC Technology","authors":"Robert B. Kargbo*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0017910.1021/acsmedchemlett.5c00179","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00179https://doi.org/10.1021/acsmedchemlett.5c00179","url":null,"abstract":"<p >KRAS mutations drive approximately 25% of human cancers, with KRAS G12D being the most prevalent and challenging to target. Recent advances have led to developing small molecule inhibitors that selectively target the active GTP-bound state of KRAS G12D, blocking downstream signaling and oncogenic activity. These compounds show strong therapeutic potential.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"746–747 746–747"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic Variation in Drug Targets: Are We Ready for the Era of Precision Medicinal Chemistry? 药物靶点的遗传变异：我们准备好进入精准药物化学时代了吗？
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 DOI: 10.1021/acsmedchemlett.5c0015310.1021/acsmedchemlett.5c00153
Clinton G. L. Veale,  and , Adrienne L. Edkins, 
{"title":"Genetic Variation in Drug Targets: Are We Ready for the Era of Precision Medicinal Chemistry?","authors":"Clinton G. L. Veale,&nbsp; and ,&nbsp;Adrienne L. Edkins,&nbsp;","doi":"10.1021/acsmedchemlett.5c0015310.1021/acsmedchemlett.5c00153","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00153https://doi.org/10.1021/acsmedchemlett.5c00153","url":null,"abstract":"<p >Natural genetic variations profoundly impact drug target interactions causing variations in in vitro biological data. The overall occurrence or “rare genetic variation” is common and enriched within population groups. Incorporating population-level genetic information earlier into the drug discovery pipeline would allow medicinal chemists to contribute to the precision medicine movement, designing drugs with more population relevance.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"706–710 706–710"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsmedchemlett.5c00153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting KRAS G12D Mutations: Advances in Small Molecule Inhibitors and PROTAC Technology. 靶向KRAS G12D突变：小分子抑制剂和PROTAC技术的进展
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 eCollection Date: 2025-05-08 DOI: 10.1021/acsmedchemlett.5c00179
Robert B Kargbo
{"title":"Targeting KRAS G12D Mutations: Advances in Small Molecule Inhibitors and PROTAC Technology.","authors":"Robert B Kargbo","doi":"10.1021/acsmedchemlett.5c00179","DOIUrl":"10.1021/acsmedchemlett.5c00179","url":null,"abstract":"<p><p>KRAS mutations drive approximately 25% of human cancers, with KRAS G12D being the most prevalent and challenging to target. Recent advances have led to developing small molecule inhibitors that selectively target the active GTP-bound state of KRAS G12D, blocking downstream signaling and oncogenic activity. These compounds show strong therapeutic potential.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"746-747"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers 使用-受体阻滞剂减少DMT的心血管副作用
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 DOI: 10.1021/acsmedchemlett.5c0018010.1021/acsmedchemlett.5c00180
Robert B. Kargbo*, 
{"title":"Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers","authors":"Robert B. Kargbo*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0018010.1021/acsmedchemlett.5c00180","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00180https://doi.org/10.1021/acsmedchemlett.5c00180","url":null,"abstract":"<p >DMT induces rapid antidepressant effects, but acute sympathomimetic side effects, particularly hypertension and tachycardia, limit its use. This study describes coformulations with short-acting beta-blockers or nitrates, matched to DMT’s pharmacokinetics, to mitigate peripheral cardiovascular risks without compromising central therapeutic action, facilitating safer psychedelic therapy in vulnerable populations.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"743–745 743–745"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers. 使用-受体阻滞剂减少DMT的心血管副作用。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 eCollection Date: 2025-05-08 DOI: 10.1021/acsmedchemlett.5c00180
Robert B Kargbo
{"title":"Reducing Cardiovascular Side Effects of DMT Using Beta-Blockers.","authors":"Robert B Kargbo","doi":"10.1021/acsmedchemlett.5c00180","DOIUrl":"10.1021/acsmedchemlett.5c00180","url":null,"abstract":"<p><p>DMT induces rapid antidepressant effects, but acute sympathomimetic side effects, particularly hypertension and tachycardia, limit its use. This study describes coformulations with short-acting beta-blockers or nitrates, matched to DMT's pharmacokinetics, to mitigate peripheral cardiovascular risks without compromising central therapeutic action, facilitating safer psychedelic therapy in vulnerable populations.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"743-745"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies. 用裸盖菇素治疗幻肢痛：与自适应感觉技术的整合。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 eCollection Date: 2025-05-08 DOI: 10.1021/acsmedchemlett.5c00182
Robert B Kargbo
{"title":"Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies.","authors":"Robert B Kargbo","doi":"10.1021/acsmedchemlett.5c00182","DOIUrl":"10.1021/acsmedchemlett.5c00182","url":null,"abstract":"<p><p>Psilocybin demonstrates a clinically meaningful reduction in phantom and residual limb pain. Adaptive sensory environments (ASEs) separately offer biosensor-guided modulation of psychological states during psychoactive therapy. This Patent Highlight explores the pharmacological findings of a psilocybin trial and discusses future integration with ASE systems to precision and scale psychedelic-assisted interventions.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"738-739"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies 用裸盖菇素治疗幻肢痛：与自适应感觉技术的整合
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-10 DOI: 10.1021/acsmedchemlett.5c0018210.1021/acsmedchemlett.5c00182
Robert B. Kargbo*, 
{"title":"Targeting Phantom Pain with Psilocybin: Toward Integration with Adaptive Sensory Technologies","authors":"Robert B. Kargbo*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0018210.1021/acsmedchemlett.5c00182","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00182https://doi.org/10.1021/acsmedchemlett.5c00182","url":null,"abstract":"<p >Psilocybin demonstrates a clinically meaningful reduction in phantom and residual limb pain. Adaptive sensory environments (ASEs) separately offer biosensor-guided modulation of psychological states during psychoactive therapy. This Patent Highlight explores the pharmacological findings of a psilocybin trial and discusses future integration with ASE systems to precision and scale psychedelic-assisted interventions.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"738–739 738–739"},"PeriodicalIF":3.5,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel Indole and Pyrrolopyridine Derivatives as GPR17 Modulators for Treating Multiple Sclerosis. 新型吲哚和吡咯吡啶衍生物作为GPR17调节剂治疗多发性硬化。
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-09 eCollection Date: 2025-05-08 DOI: 10.1021/acsmedchemlett.5c00176
Ram W Sabnis
{"title":"Novel Indole and Pyrrolopyridine Derivatives as GPR17 Modulators for Treating Multiple Sclerosis.","authors":"Ram W Sabnis","doi":"10.1021/acsmedchemlett.5c00176","DOIUrl":"10.1021/acsmedchemlett.5c00176","url":null,"abstract":"<p><p>Provided herein are novel indole and pyrrolopyridine derivatives as GPR17 modulators, pharmaceutical compositions, use of such compounds in treating multiple sclerosis, and processes for preparing such compounds.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"736-737"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted Degradation of BCL6 Using Novel Bifunctional Degraders: A New Therapeutic Strategy for BCL6-Positive Cancers 利用新型双功能降解剂靶向降解BCL6: BCL6阳性癌症的新治疗策略
IF 3.5 3区 医学
ACS Medicinal Chemistry Letters Pub Date : 2025-04-09 DOI: 10.1021/acsmedchemlett.5c0018110.1021/acsmedchemlett.5c00181
Robert B. Kargbo*, 
{"title":"Targeted Degradation of BCL6 Using Novel Bifunctional Degraders: A New Therapeutic Strategy for BCL6-Positive Cancers","authors":"Robert B. Kargbo*,&nbsp;","doi":"10.1021/acsmedchemlett.5c0018110.1021/acsmedchemlett.5c00181","DOIUrl":"https://doi.org/10.1021/acsmedchemlett.5c00181https://doi.org/10.1021/acsmedchemlett.5c00181","url":null,"abstract":"<p >BCL6 overexpression drives lymphomagenesis and immune evasion in B-cell malignancies. This Patent Highlight presents novel bifunctional degraders targeting BCL6, demonstrating high potency and selectivity. These degraders induce BCL6 degradation via a PROTAC-based mechanism, resulting in apoptosis and tumor regression in BCL6-positive cancers. This targeted approach offers enhanced efficacy and therapeutic potential.</p>","PeriodicalId":20,"journal":{"name":"ACS Medicinal Chemistry Letters","volume":"16 5","pages":"740–742 740–742"},"PeriodicalIF":3.5,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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